1. Field of the Invention
The invention pertains to the field of the systems for exchanging in a controlled way liquids with micro-sized samples of material like biological cells, or the like. It refers to a probe arrangement for exchanging in a controllable way liquids with micro-sized samples of material like biological cells, especially in connection with a scanning probe microscope, according to the preamble of claim 1.
2. Discussion of Related Art
Background of the invention It is well-known in the art to use scanning probe microscopes, especially in the form of scanning force microscopes, to examine and non-destructively characterize surfaces of a specimen (see for example U.S. Pat. No. B2-7,114,405). The mounting of probes utilized for examining a specimen is of decisive significance for the operation of a scanning probe microscope. In any scanning probe microscope, the probe must be secured in such a way that a respective measured physical variable can be detected in dependence upon a distance between the specimen and a measuring tip of the probe. One type of scanning probe microscopy is scanning force microscopy with which a spring pole is used as the probe, normally referred to as a cantilever. There is a measuring tip at one end of the cantilever. The probe (cantilever) preferably consists of silicon, but other materials may be used as well, such as silicon nitride or diamond. As a rule, the cantilever, including its measuring tip, is mounted on a substrate, sometimes referred to as base or probe holder. Adequate mounting of the cantilever must meet the corresponding diverse requirements as well. Two kinds of mounting the cantilever in a scanning probe microscope are known in the art. With one of them, the cantilever is either attached by gluing or retained by means of a liquid which has adhesive properties. The second type of known mounting is fully mechanical, usually implemented by means of a spring. Fastening of the cantilever by means of an adhesive is unsuitable for many scanning probe microscopes since the most frequently applied adhesive materials produce a long lasting bond between the probe and a retaining member to which the probe is to be fixed, a bond which can be severed only by taking recourse to solvents. Besides, the use of adhesive materials is very critical for operating scanning probe microscopes in liquids because the liquid within which the probe is located may undergo chemical changes caused by interaction with the adhesive material. For this reason, mechanical fastening by means of some spring retention often is selected (see FIG. 1 of the present application).
It is also well-known in the art (see EP-A1-I 990 626), to use a cantilevered probe arrangement including micro channels that may be controllable by a drive for performing analysis and/or manipulation of micro-sized samples of material, in, e.g., a fluid environment constituting, for example, biological material. The cantilever probe tip may for example be employed to perform electrophysiological tests in accordance to, for example, various modes such as a static and a scanning mode of samples of biological material such as biological tissue; an individual cell as well as elements thereof including vesicles, cell membrane and portions thereof, lipid bilayers and artificial lipid bilayers. The micro-channels enable the release of fluids and the collection of samples in the very range where the electrophysiological tests are performed. One of the main applications of such a cantilever probe arrangement is associated to cell biology, such as intracellular injection or sampling of the cytoplasm, extracellular drug release or sampling of the environmental buffer in relative proximity close to the cell by means of the force-controlled cantilever probe tip.
However, in using the micro fabricated cantilevers with their internal micro channels with a scanning probe microscope, one has to mount the cantilevers on a suitable probe holder, such that the cantilever is securely fixed to said probe holder in a correct position. At the same time, a liquid-tight connection between the cantilever and the probe holder has to be established, so that liquid can be exchanged under a defined pressure between an (external or internal) liquid reservoir and the sample to be probed. This is a difficult task in the normal environment of a laboratory, and may result in damaging the cantilever or failing to achieve a pressure-tight connection between the cantilever and the probe holder.